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      Neoantigens and their potential applications in tumor immunotherapy

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          Abstract

          The incidence of malignant tumors is increasing, the majority of which are associated with high morbidity and mortality rates worldwide. The traditional treatment method for malignant tumors is surgery, coupled with radiotherapy or chemotherapy. However, these therapeutic strategies are frequently accompanied with adverse side effects. Over recent decades, tumor immunotherapy shown promise in demonstrating notable efficacy for the treatment of cancer. With the development of sequencing technology and bioinformatics algorithms, neoantigens have become compelling targets for cancer immunotherapy due to high levels of immunogenicity. In addition, neoantigen-based vaccines have demonstrated potential for cancer therapy, primarily by augmenting T-cell responses. Neoantigens have also been shown to be effective in immune checkpoint blockade therapy. Therefore, neoantigens may serve to be predictive biomarkers and synergistic treatment targets in cancer immunotherapy. The aim of the present review was to provide an overview of the recent progress in the classification, screening and clinical application of neoantigens for cancer therapy.

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          Most cited references95

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          Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

          An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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            Oncology meets immunology: the cancer-immunity cycle.

            The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer. Copyright © 2013 Elsevier Inc. All rights reserved.
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              mRNA vaccines — a new era in vaccinology

              mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2022
                21 January 2022
                21 January 2022
                : 23
                : 3
                : 88
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Weifang Medical University, Weifang, Shandong 261053, P.R. China
                [2 ]Department of Orthopedic, The 80th Group Army Hospital of Chinese People's Liberation Army, Weifang, Shandong 261021, P.R. China
                Author notes
                Correspondence to: Dr Hong Li, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Weifang Medical University, 7166 West Baotong Road, Weifang, Shandong 261053, P.R. China, E-mail: lh@ 123456wfmc.edu.cn
                [*]

                Contributed equally

                Article
                OL-23-03-13208
                10.3892/ol.2022.13208
                8805178
                35126730
                be1f32cc-299f-42d6-9655-f1cbb8fb8602
                Copyright: © Fang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 13 September 2021
                : 04 January 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81870237
                Funded by: Foundation of Health Commission of Weifang
                Award ID: wfwsjk_2019_025
                Funded by: Research Project of Shandong Provincial Education Department
                Award ID: J14LK12
                Funded by: Weifang Medical University Doctoral Startup Fund
                The present review was supported by the National Natural Science Foundation of China (grant no. 81870237), the Foundation of Health Commission of Weifang (grant no. wfwsjk_2019_025), the Research Project of Shandong Provincial Education Department (grant no. J14LK12) and the Weifang Medical University Doctoral Startup Fund.
                Categories
                Review

                Oncology & Radiotherapy
                neoantigen,immunotherapy,tumor vaccine,immune checkpoint blockade
                Oncology & Radiotherapy
                neoantigen, immunotherapy, tumor vaccine, immune checkpoint blockade

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